Adhesion formation is a major post-surgical complication with no practical solution. The incidence of adhesion formation following surgery approaches 100 percent, according to some sources, with a clinically significant complication rate of about 5 to 10 percent, depending on the type of surgery. Among such complications are bowel obstruction, infertility, and pain. Occasionally, adhesions necessitate a second operative procedure to remove the adhesion, which may in turn further aggravate the problem.
Because of the seriousness of the problem, much medical research has been performed in efforts to find ways to combat adhesions. See, for instance, Stangel et al., "Formation and Prevention of Postoperative Abdominal Adhesions", the Journal of Reproductive Medicine, Vol. 29, No. 3, March 1984 (pp. 143-156), and diZerega, "The Cause and Prevention of Postsurgical Adhesions", published by Pregnancy Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Building 18, Room 101, Bethesda, Md. 20205. Among the approaches that have been tried for preventing post-surgical adhesion are the following:
Systemic administration of ibuprofen (e.g., see Singer, U.S. Pat. No. 4,346,108); PA0 Parenteral administration of antihistamines, corticosteroids, and antibiotics; PA0 Intraperitoneal administration of dextran solution and of polyvinylpyrrolidone solution; and PA0 Systemic administration of oxyphenbutazone, a non-steroidal anti-inflammatory drug that acts by inhibiting prostaglandin production. PA0 Ascherl et al., PREVENTION OF INTRAPERITONEAL ADHESIONS WITH A FIBRINOLYTIC, Medwelt, 34, No. 13/83, pp. 410-415; PA0 Mund-Hoym et al., PREVENTION OF POSTOPERATIVE ADHESIONS-AN ANIMAL STUDY, Geburtsh, u. Franenheilk, 44 (1984), pp. 463-467; and PA0 Minju et al., ANIMAL STUDIES ON THE PREVENTION OF ADHESION AND ADHESIVE INTESTINAL OBSTRUCTION AFTER ABDOMINAL OPERATIONS IN RATS, Acta Acadeniae Medicinae Wuhan, 3, (2), pp. 77-83. PA0 Holtz, "Prevention of Postoperative Adhesions", The Journal of Reproductive Medicine, Vol. 24, No. 4, April 1980, pp. 141-146, esp. p. 144; and PA0 Rivkind et al., Eur. Surg. Res. (Switzerland), 1985, Vol. 17, No. 4, pp. 254-8. PA0 a lipid or mixture of lipids such as lecithin or other phospholipid, which may be mixed with cholesterol or other lipoid substance, is dissolved in a substantially water-immiscible organic solvent such as diethyl ether; and PA0 an aqueous phase containing the material to be encapsulated (in this case, t-PA) is added to the lipid solution, and the mixture is agitated as by exposing it to ultrasonic sound waves (sonicated). Preferably, the organic solvent is removed during sonication, as by use of heat or vacuum or both, although in some cases the solvent can be removed after the sonication. This procedure typically produces a unilamellar vesicle. PA0 1. No adhesions PA0 2. Filmy adhesions (separable) PA0 3. Mild adhesions (not separable--covering up to about 35% of the test area) PA0 4. Moderate adhesions (not separable--covering about 35 to 60% of the test area) PA0 5. Severe adhesions (not separable--covering greater than about 60% of the test area)
Corticosteroids have been administered intraperitoneally as well as systemically in efforts to prevent adhesions. (See the Stangel et al. article, cited above, on p. 147, as well as the articles cited therein.) Some studies have questioned the efficacy of corticosteroids in adhesion prevention. In high doses, these materials may suppress the immune system and interfere with wound healing. Therefore, the use of corticosteroids does not seem to be an acceptable solution to the post-operative adhesion problem.